PROPAGATION OF A UNIQUE V^σ1-BEARING V^σT CELLS CLONE WITHIN GRAFT INFILTRATES OF HUMAN LIVER TRANSPLANTATION TOLERANCE-IMMUNOPRIVILEGED LIVER SPECIFIC ?-

本文报道了肝移植耐受患者外周血中V^σ-1携带型Y^σT细胞(V^σ-1细胞)较V^σ-2携带型Y^σT细胞(V^σ-2细胞)占优势，V^σ-1细胞是正常人Y^DNA T细胞的一个亚群。我们进一步检测了LTX耐受患者移植物浸润液中V、σ-1Cells/V、σ-2Cells(V、σ-1/V、σ-2)的比例和V、σ-1TCR链的序列。为了阐明V、σ-1细胞是否参与了雷公藤毒素的免疫应答，我们还对高免疫原性的肠道毒素进行了研究。方法对LTX(N=18)和肠TX(ITX)(N=3)(Gr-to1)术后无免疫抑制或免疫抑制程度最低的移植物功能良好的患者进行常规活检。提取总RNA，合成c DNA。用实时定量聚合酶链式反应检测V^σ1和V^σ2基因的表达，并分析V^σ1TCR链上的CDR3序列。将结果与慢性排斥移植肝(Gr-CRN=9)和正常肝脏(Gr-NOR N=6)和ITX患者的自然肠道(Gr-NAT N=2)进行比较。结果Gr-TOL组LTX；V、σ1/V、σ-2比值最高，与Gr-CR、Gr-NOR组比较差异有统计学意义(P<0.05)。Gr-TOL的V、σ-1序列向单/寡克隆方向移动，而Gr-CR则向多克隆方向移动。9例耐受患者中有8例观察到1个显性序列，而Gr-CR中没有发现相同的序列。与LTX不同，Gr-Tol和Gr-NAT的V、σ1/V、σ2比值无差异。在Gr-TOL患者中未观察到V、σ-1序列或任何常见序列的单克隆/寡克隆移位。结论耐受肝移植物中存在独特的V？σ-1T细胞克隆，而耐受肠移植物中未见该细胞克隆。我们假设这种传播是肝脏抗原选择的，并与肝脏TX的免疫排斥机制有关。

We reported that V^σ1bearing Y^σT cells (V^σ1 cells), which represent a minor subset of Y^σT cells in normal individuals, predominate over V^σ 2bearing Y^σT cells (V^σ2 cells) in peripheral blood of tolerant patients after liver transplantation (LTx). We further examined LTx tolerant patients for V^σ1 cells/V^σ2 cells (V^σ1/V^σ2) ratio and sequence in V^σ1 TCR chains in graft infiltrates. To elucidate whether V^σ1 cells are responsible for immunoprivilege of LTx, highly immunogenic intestinal Tx (ITx) was studied in addition. Method Protocol biopsy was performed in patients whose grafts were functioning well despite the absence of or minimum immunosuppression after LTx (N= 18) and intestinal Tx (ITx) (N=3)(Gr-To1). Total RNA was extracted to synthesize cDNA. V^σ1 and V^σ2 gene expressions were quantified by real-time PCR, and CDR3 sequence in V^σ1 TCR chains was analyzed. The results were compared to those of chronically rejecting grafts (Gr-CR N=9) and normal liver (Gr-Nor N=6) in LTx and native intestines of the patients (Gr-Nat N=2) in ITx. Results LTx ; V^σ1/V^σ2 ratio was the highest in Gr-Tol, compared to those in Gr-CR and Gr-Nor (p<0.05). Sequences of V^σ1 in Gr-Tol were shifted towards mono-/oligo-clonal pattern, while polyclonal in Gr-CR. One dominant sequence was observed in 8 out of 9 tolerant patients but identical sequence was not seen in Gr-CR. ITx ; Unlike LTx, there was no difference between V^σ1/V^σ2 ratio of Gr-Tol and Gr-Nat. Neither mono-/oligo-clonal shift of V^σ1 sequence nor any common sequence was observed among patients in Gr-Tol. Conclusion A unique V^σ1T cell clone propagated within tolerant liver graft but not tolerant intestinal graft. We hypothesize that this propagation is liver-antigen-selected and associated with a mechanism of immunoprivilege of liver Tx.